Diosgenin, the main aglycon of fenugreek, inhibits lxrα activity in hepg2 cells and decreases plasma and hepatic triglycerides in obese diabetic mice1-3

Journal of Nutrition

Volumn 141, Issue 1, 2011, Pages 17-23

  Uemura, Taku ^a   Goto, Tsuyoshi ^a   Kang, Min Sook ^a,c   Mizoguchi, Noriko ^a   Hirai, Shizuka ^a   Lee, Joo Yong ^a   Nakano, Yuki ^b   Shono, Jinji ^b   Hoshino, Shohei ^b   Taketani, Keiko ^b   Tsuge, Nobuaki ^b   Narukami, Toshihiko ^b   Makishima, Makoto ^c   Takahashi, Nobuyuki ^a   Kawada, Teruo ^a  

^a KYOTO UNIVERSITY   (Japan)

^b House Foods Corporation   (Japan)

^c NIHON UNIVERSITY SCHOOL OF MEDICINE   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

AGLYCONE; DIOSGENIN; LIVER X RECEPTOR ALPHA; LUCIFERASE; MESSENGER RNA; SAPONIN; TRIACYLGLYCEROL;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CELL STRAIN HEPG2; CONTROLLED STUDY; DIABETIC OBESITY; DRUG STRUCTURE; FENUGREEK; GEL MOBILITY SHIFT ASSAY; GENE EXPRESSION; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HYDROLYSIS; LIPID DIET; LIPID METABOLISM; LIPOGENESIS; LIQUID CHROMATOGRAPHY; MALE; MOUSE; NONHUMAN; TANDEM MASS SPECTROMETRY; TRANSACTIVATION; TRIACYLGLYCEROL BLOOD LEVEL;

ANIMALS; DIABETES MELLITUS; DIOSGENIN; HEP G2 CELLS; HUMANS; HYPERLIPIDEMIAS; LIVER; MALE; MICE; MICE, OBESE; ORPHAN NUCLEAR RECEPTORS; PHYTOTHERAPY; RNA, MESSENGER; STEROL REGULATORY ELEMENT BINDING PROTEIN 1; TRIGLYCERIDES; TRIGONELLA;

MUS; TRIGONELLA FOENUM-GRAECUM;

EID: 78650498453     PISSN: 00223166     EISSN: 15416100     Source Type: Journal    
DOI: 10.3945/jn.110.125591     Document Type: Article

References (38)

1. Kahn BB, Flier JS. Obesity and insulin resistance. J Clin Invest. 2000; 106:473-81.
2. Horton JD, Goldstein JL, Brown MS. SREBPs: Transcriptional mediators of lipid homeostasis. Cold Spring Harb Symp Quant Biol. 2002; 67:491-8.
3. Roepstorff C, Halberg N, Hillig T, Saha AK, Ruderman NB, Wojtaszewski JF, Richter EA, Kiens B. Malonyl-CoA and carnitine in regulation of fat oxidation in human skeletal muscle during exercise. Am J Physiol Endocrinol Metab. 2005;288:E133-42.
4. Tugwood JD, Issemann I, Anderson RG, Bundell KR, McPheat WL, Green S. The mouse peroxisome proliferator activated receptor recognizes a response element in the 59 flanking sequence of the rat acyl CoA oxidase gene. EMBO J. 1992;11:433-9.
5. Chen G, Liang G, Ou J, Goldstein JL, Brown MS. Central role for liver X receptor in insulin-mediated activation of Srebp-1c transcription and stimulation of fatty acid synthesis in liver. Proc Natl Acad Sci USA. 2004;101:11245-50.
6. Janowski BA, Willy PJ, Devi TR, Falck JR, Mangelsdorf DJ. An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha. Nature. 1996;383:728-31.
7. Lehmann JM, Kliewer SA, Moore LB, Smith-Oliver TA, Oliver BB, Su JL, Sundseth SS, Winegar DA, Blanchard DE, et al. Activation of the nuclear receptor LXR by oxysterols defines a new hormone response pathway. J Biol Chem. 1997;272:3137-40.
8. Wiebel FF, Gustafsson JA. Heterodimeric interaction between retinoid X receptor alpha and orphan nuclear receptor OR1 reveals dimerization- induced activation as a novel mechanism of nuclear receptor activation. Mol Cell Biol. 1997;17:3977-86.
9. Willy PJ, Mangelsdorf DJ. Unique requirements for retinoid-dependent transcriptional activation by the orphan receptor LXR. Genes Dev. 1997;11:289-98.
10. Edwards PA, Kast HR, Anisfeld AM. BAREing it all: The adoption of LXR and FXR and their roles in lipid homeostasis. J Lipid Res. 2002; 43:2-12.
11. Morton JF. Mucilaginous plants and their uses in medicine. J Ethnopharmacol. 1990;29:245-66.
12. Basch E, Ulbricht C, Kuo G, Szapary P, Smith M. Therapeutic applications of fenugreek. Altern Med Rev. 2003;8:20-7.
13. Annida B, Stanely Mainzen Prince P. Supplementation of fenugreek leaves lower lipid profile in streptozotocin-induced diabetic rats. J Med Food. 2004;7:153-6.
14. Raju J, Bird RP. Alleviation of hepatic steatosis accompanied by modulation of plasma and liver TNF-alpha levels by Trigonella foenum graecum (fenugreek) seeds in Zucker obese (fa/fa) rats. Int J Obese (Lond). 2006;30:1298-307.
15. Hannan JM, Rokeya B, Faruque O, Nahar N, Mosihuzzaman M, Azad Khan AK, Ali L. Effect of soluble dietary fibre fraction of Trigonella foenum graecum on glycemic, insulinemic, lipidemic and platelet aggregation status of Type 2 diabetic model rats. J Ethnopharmacol. 2003;88:73-7.
16. Raju J, Gupta D, Rao AR, Yadava PK, Baquer NZ. Trigonellafoenum graecum (fenugreek) seed powder improves glucose homeostasis in alloxan diabetic rat tissues by reversing the altered glycolytic, gluconeogenic and lipogenic enzymes. Mol Cell Biochem. 2001;224:45-51.
17. Stark A, Madar Z. The effect of an ethanol extract derived from fenugreek (Trigonella foenum-graecum) on bile acid absorption and cholesterol levels in rats. Br J Nutr. 1993;69:277-87.
18. Trinh HT, Han SJ, Kim SW, Lee YC, Kim DH. Bifidus fermentation increases hypolipidemic and hypoglycemic effects of red ginseng. J Microbiol Biotechnol. 2007;17:1127-33.
19. Li H, Wang QJ, Zhu DN, Yang Y. A triterpene saponin of Polygala aureocauda Dunn, exerts hypolipidemic effect on hyperlipidemic mice. Phytother Res. 2008;22:159-64.
20. Kawada T, Hagihara K, Iwai K. Effects of capsaicin on lipid metabolism in rats fed a high fat diet. J Nutr. 1986;116:1272-8.
21. Uemura T, Hirai S, Mizoguchi N, Goto T, Lee JY, Taketani K, Nakano Y, Shono J, Hoshino S, et al. Diosgenin present in fenugreek improves glucose metabolism by promoting adipocyte differentiation and inhibiting inflammation in adipose tissues. Mol Nutr Food Res. 2010;54:1596-608.
22. Bligh EG, Dyer WJ. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959;37:911-7.
23. Takahashi N, Kawada T, Goto T, Yamamoto T, Taimatsu A, Matsui N, Kimura K, Saito M, Hosokawa M, et al. Dual action of isoprenols from herbal medicines on both PPAR-gamma and PPARalpha in 3T3-L1 adipocytes and HepG2 hepatocytes. FEBS Lett. 2002;514: 315-22.
24. Goto T, Takahashi N, Kato S, Egawa K, Ebisu S, Moriyama T, Fushiki T, Kawada T. Phytol directly activates peroxisome proliferator-activated receptor alpha (PPAR-alpha) and regulates gene expression involved in lipid metabolism in PPAR-alpha-expressing HepG2 hepatocytes. Biochem Biophys Res Commun. 2005;337:440-5.
25. Takahashi N, Kawada T, Yamamoto T, Goto T, Taimatsu A, Aoki N, Kawasaki H, Taira K, Yokoyama KK, et al. Overexpression and ribozyme-mediated targeting of transcriptional coactivators CBP and p300 revealed their indispensable roles in adipocyte differentiation through the regulation of peroxisome proliferator-activated receptor gamma. J Biol Chem. 2002;277:16906-12.
26. Hirai S, Kim YI, Goto T, Kang MS, Yoshimura M, Obata A, Yu R, Kawada T. Inhibitory effect of naringenin chalcone on inflammatory changes in the interaction between adipocytes and macrophages. Life Sci. 2007;81:1272-9.
27. Kaneko E, Matsuda M, Yamada Y, Tachibana Y, Shimomura I, MakishimaM. Induction of intestinal ATP-binding cassette transporters by a phytosterol-derived liver X receptor agonist. J Biol Chem. 2003; 278:36091-8.
28. Takahashi N, Kawada T, Goto T, Kim CS, Taimatsu A, Egawa K, Yamamoto T, Jisaka M, Nishimura K, et al. Abietic acid activates peroxisome proliferator-activated receptor-gamma (PPAR-gamma) in RAW264.7 macrophages and 3T3-L1 adipocytes to regulate gene expression involved in inflammation and lipid metabolism. FEBS Lett. 2003;550:190-4.
29. Kuroyanagi K, Kang MS, Goto T, Hirai S, Ohyama K, Kusudo T, Yu R, Yano M, Sasaki T, et al. Citrus auraptene acts as an agonist for PPARs and enhances adiponectin production and MCP-1 reduction in 3T3-L1 adipocytes. Biochem Biophys Res Commun. 2008;366:219-25.
30. Ide T, Shimano H, Yoshikawa T, Yahagi N, Amemiya-Kudo M, Matsuzaka T, Nakakuki M, Yatoh S, Iizuka Y, et al. Cross-talk between peroxisome proliferator-activated receptor (PPAR) alpha and liver X receptor (LXR) in nutritional regulation of fatty acid metabolism. II. LXRs suppress lipid degradation gene promoters through inhibition of PPAR signaling. Mol Endocrinol. 2003;17:1255-67.
31. Taylor WG, Zamanr MS, Mir Z, Mir PS, Acharya SN, Mears GJ, Elder JL. Analysis of steroidal sapogenins from Amber fenugreek (Trigonella foenum-graecum) by capillary gas chromatography and combined gas chromatography mass spectrometry. J Agric Food Chem. 1997;45:753-9.
32. Browning JD, Horton JD. Molecular mediators of hepatic steatosis and liver injury. J Clin Invest. 2004;114:147-52.
33. Shimomura I, Bashmakov Y, Horton JD. Increased levels of nuclear SREBP-1c associated with fatty livers in two mouse models of diabetes mellitus. J Biol Chem. 1999;274:30028-32.
34. Taylor WG, Elder JL, Chang PR, Richards KW. Microdetermination of diosgenin from fenugreek (Trigonella foenum-graecum) seeds. J Agric Food Chem. 2000;48:5206-10.
35. Kim CM, Son KH, Kim SH, Kim HP. Steroidal sapogenin contents in some domestic plants. Arch Pharm Res. 1991;14:305-10.
36. Brown MS, Goldstein JL. A proteolytic pathway that controls the cholesterol content of membranes, cells, and blood. Proc Natl Acad Sci USA. 1999;96:11041-8.
37. Kalaany NY, Gauthier KC, Zavacki AM, Mammen PP, Kitazume T, Peterson JA, Horton JD, Garry DJ, Bianco AC, et al. LXRs regulate the balance between fat storage and oxidation. Cell Metab. 2005;1:231-44.
38. Yoshikawa T, Shimano H, Yahagi N, Ide T, Amemiya-Kudo M, Matsuzaka T, Nakakuki M, Tomita S, Okazaki H, et al. Polyunsaturated fatty acids suppress sterol regulatory element-binding protein 1c promoter activity by inhibition of liver X receptor (LXR) binding to LXR response elements. J Biol Chem. 2002;277:1705-11.